Studies are underway to ascertain information on: (a) the effects of cannabidiol (CBD), a nontoxic constituent of marijuana, in combination with antiepileptic drugs on experimentally induced seizure models; (b) mechanisms of action of the anticonvulsant effects of CBD; (c) behavioral convulsant effects of marijuana cannabinoids and drug antagonists of cannabinoid induced seizures; (d) mechanisms of action of behavioral and electroencephalographic (EEG) convulsive effects of cannabinoids. The combined effects of CBD and antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, chlordiazepoxide, clonazepam, ethosuximide and trimethadione) on maximal electroshock seizure (MES) and audiogenic seizures (AS) will be assessed in rats. Further, selected combinations of CBD with ethosuximide and trimethadione will be tested on other seizure types (e.g., pentylenetetrazol). Moreover, the possible involvement of brain neurochemicals (e.g., catecholamines, serotonin, GABA, acetylcholine, glycine) in the anticonvulsant action of CBD will also be studied. It is anticipated that these studies will provide important predictive information on the potential therapeutic spectrum and usefulness of CBD and basic information on the mechanism of the anticonvulsant action of the cannabinoid in seizure states. We have previously discovered a strain of New Zealand White rabbit that exhibits behavioral convulsions after giving low i.v. doses (0.5 mg/kg or less) of delta 9 THC, the major psychoactive component of marijuana. Using quantitative EEG and behavioral monitoring techniques, the effects of several cannabinoids (delta 9 THC, CBD, CBN, etc.) will be studied with regard to possible brain loci and mechanisms (e.g., involvement of GABA, serotonin, catecholamines, etc.). Further, effects of potential drug antagonists to delta 9 THC induced seizures will also be investigated. These studies should yield valuable mechanistic information on this unique paradigm of the stimulant effects of cannabinoids. BIBLIOGRAPHIC REFERENCES: Consroe, P. and Jones, B.: LSD-neuroleptic drug interactions in rabbits. The Pharmacologist 18(2): 143, 1976. Laird, H., Consroe, P. and Straussner, A.: Anticonvulsant drug comparisons in audiogenic and non-audiogenic rats. The Pharmacologist 18(2):136, 1976.